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Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility.

Protein kinase C (PKC) alpha has been implicated in beta1 integrin-mediated cell migration. Stable expression of PKCalpha is shown here to enhance wound closure. This PKC-driven migratory response directly correlates with increased C-terminal threonine phosphorylation of ezrin/moesin/radixin (ERM) at the wound edge. Both the wound migratory response and ERM phosphorylation are dependent upon the catalytic function of PKC and are susceptible to inhibition by phosphatidylinositol 3-kinase blockade. Upon phorbol 12,13-dibutyrate stimulation, green fluorescent protein-PKCalpha and beta1 integrins co-sediment with ERM proteins in low-density sucrose gradient fractions that are enriched in transferrin receptors. Using fluorescence lifetime imaging microscopy, PKCalpha is shown to form a molecular complex with ezrin, and the PKC-co-precipitated endogenous ERM is hyperphosphorylated at the C-terminal threonine residue, i.e. activated. Electron microscopy showed an enrichment of both proteins in plasma membrane protrusions. Finally, overexpression of the C-terminal threonine phosphorylation site mutant of ezrin has a dominant inhibitory effect on PKCalpha-induced cell migration. We provide the first evidence that PKCalpha or a PKCalpha-associated serine/threonine kinase can phosphorylate the ERM C-terminal threonine residue within a kinase-ezrin molecular complex in vivo.

Pubmed ID: 11387207

Authors

  • Ng T
  • Parsons M
  • Hughes WE
  • Monypenny J
  • Zicha D
  • Gautreau A
  • Arpin M
  • Gschmeissner S
  • Verveer PJ
  • Bastiaens PI
  • Parker PJ

Journal

The EMBO journal

Publication Data

June 1, 2001

Associated Grants

None

Mesh Terms

  • Amino Acid Substitution
  • Antigens, CD29
  • Breast Neoplasms
  • Cell Membrane
  • Cell Movement
  • Chromones
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Isoenzymes
  • Kinetics
  • Luminescent Proteins
  • Microscopy, Confocal
  • Morpholines
  • Mutagenesis, Site-Directed
  • Phorbol 12,13-Dibutyrate
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Phosphorylation
  • Phosphothreonine
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Recombinant Fusion Proteins
  • Tumor Cells, Cultured
  • Wound Healing